Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana

Two-pore channels (TPCs) comprise a subfamily (TPC1-3) of eukaryotic voltage-and ligand-gated cation channels1,2 that contain two non-equivalent tandem pore-forming subunits that then dimerize to form quasi-tetramers. Found in vacuolar3 or endolysosomal4 membranes, they regulate the conductance of sodium5 and calcium3,6 ions, intravesicular pH5, trafficking7 and excitability8,9. TPCs are activated by a decrease in transmembrane potential1,3,9,10, an increase in cytosolic calcium concentrations1,10, and inhibited by luminal low pH, and calcium11, ...